MOTIFS AND DOMAINS

A motif is used in multiple techniques to generate the signature type of a protein. Each technique begins with a sequence alignment of many proteins, and then can either center in on one or multiple preserved sequence regions, or one can do a full alignment of the whole protein or a certain domain.

A domain is particular functional and/or structural unit of a protein. Domains cause certain function or interaction, which defines the inherent capacity of a protein. Domains are not limited to a certain biological context since homologous domains can be found in varieties of proteins with diverse functions. [1]

Copper serves as a very common transition metal in living organisms despite the fact that loose copper ions in an organism are extremely toxic. Therefore, multicopper oxidases need to control homeostasis via molecular mechanisms. [2] Generally, a substrate is oxidised by multicopper oxidases by accepting electrons at a mononuclear copper centre and moving them to a trinuclear copper centre. Dioxygen then binds to the trinuclear centre and reduces to water. [3] There are three different copper centres found in multicopper oxidases (shown in Figures 3 and 4): Type 1 (blue), 2 (normal) and 3 (coupled binuclear). [4] [5] 2, 3 or 6 of these three homologous domains make up multicopper oxidases. The domains structurally consist of a cupredoxin-like fold (a beta-sandwich made up of seven strands in two beta-sheets), organized in a Greek-key beta-barrel. [6] However, in the first domain of the blood coagulation Factor VIII (non-copper binding), even though the structure and sequence is very similar to a multicopper oxidase domain, it has actually lost its ability to bind copper. [7]

In coagulation factor VIII there are two repeated domains on the C-terminal called FA58C (protein structure found in Figure 5). The C-terminal domain on the second FA58C is known to cause phosphatidylserine-binding and necessary for activity. [8] [9] This domain creates an amphipathic alpha-helix, which binds to the membrane. [10] The two repeated domains are connected by their homologous cysteines, which link together via a disulfide bond. [11] [12] [13] Alternative splicing is present at many points in my protein sequence: B1B0G9_HUMAN, FA8_HUMAN, UPI0001AE709C, B1B0G8_HUMAN, Q14286_HUMAN, UPI0001AE709D.